Aarhus University, Aarhus, Denmark.
PLoS One. 2012;7(8):e43508. doi: 10.1371/journal.pone.0043508. Epub 2012 Aug 28.
The etiology of type-2 diabetes is only partly known, and a possible role of prenatal stress in programming offspring for insulin resistance has been suggested by animal models. Previously, we found an association between prenatal stress and type-1 diabetes. Here we examine the association between prenatal exposure to maternal bereavement during preconception and pregnancy and development of type-2 diabetes in the off-spring.
We utilized data from the Danish Civil Registration System to identify singleton births in Denmark born January 1(st) 1979 through December 31(st) 2008 (N = 1,878,246), and linked them to their parents, grandparents, and siblings. We categorized children as exposed to bereavement during prenatal life if their mothers lost an elder child, husband or parent during the period from one year before conception to the child's birth. We identified 45,302 children exposed to maternal bereavement; the remaining children were included in the unexposed cohort. The outcome of interest was diagnosis of type-2 diabetes. We estimated incidence rate ratios (IRRs) from birth using log-linear poisson regression models and used person-years as the offset variable. All models were adjusted for maternal residence, income, education, marital status, sibling order, calendar year, sex, and parents' history of diabetes at the time of pregnancy.
We found children exposed to bereavement during their prenatal life were more likely to have a type-2 diabetes diagnosis later in life (aIRR: 1.31, 1.01-1.69). These findings were most pronounced when bereavement was caused by death of an elder child (aIRR: 1.51, 0.94-2.44). Results also indicated the second trimester of pregnancy to be the most sensitive period of bereavement exposure (aIRR:2.08, 1.15-3.76).
Our data suggests that fetal exposure to maternal bereavement during preconception and the prenatal period may increase the risk for developing type-2 diabetes in childhood and young adulthood.
2 型糖尿病的病因尚不完全清楚，动物模型提示产前应激可能在胰岛素抵抗的后代编程中起作用。此前，我们发现产前应激与 1 型糖尿病之间存在关联。在这里，我们研究了在受孕前和怀孕期间产妇丧亲经历与后代 2 型糖尿病发病之间的关系。
我们利用丹麦民事登记系统的数据，确定 1979 年 1 月 1 日至 2008 年 12 月 31 日期间在丹麦出生的单胎婴儿（N=1878246），并将其与父母、祖父母和兄弟姐妹进行关联。如果母亲在受孕前一年至孩子出生期间失去了年长的孩子、丈夫或父母，我们将孩子归类为产前生活中丧亲。我们确定了 45302 名暴露于母亲丧亲的儿童；其余儿童纳入未暴露队列。感兴趣的结局是 2 型糖尿病的诊断。我们使用对数线性泊松回归模型从出生开始估计发病率比（IRR），并使用人年作为偏移量。所有模型均根据母亲居住地、收入、教育程度、婚姻状况、兄弟姐妹顺序、日历年份、性别以及父母在怀孕期间的糖尿病史进行调整。
我们发现，在产前生活中经历丧亲的儿童在以后的生活中更有可能被诊断为 2 型糖尿病（aIRR：1.31，1.01-1.69）。当丧亲是由年长孩子的死亡引起时，这些发现最为明显（aIRR：1.51，0.94-2.44）。结果还表明妊娠中期是丧亲经历最敏感的时期（aIRR：2.08，1.15-3.76）。
我们的数据表明，胎儿在受孕前和产前暴露于母亲丧亲可能会增加儿童和青年时期患 2 型糖尿病的风险。
